Focal myelin thickenings in a peripheral neuropathy associated with IgM monoclonal gammopathy

Summary Nerve biopsy in peripheral neuropathies associated with an IgM monoclonal gammopathy may occasionally display focal myelin thickenings. In a patient with such an IgM neuropathy, in whom an anti-myelin-associated glycoprotein (MAG) antibody activity was present in the serum, single-fiber preparations revealed 34% of internodes bearing myelin swellings. The morphometric, morphological and ultrastructural findings were reminiscent but not identical to those of the hereditary tomaculous neuropathy with liability to pressure palsies. Atypical features for tomacula included lack of spiralization of the redundant loops of myelin around the axons and their predominant external situation with regard to the myelin sheath. The frequent colocalization of myelin thickenings and the widening of myelin lamellae typical of IgM neuropathies, are highly suggestive of some pathogenetic link between the two abnormalities. The redundant loops of myelin in IgM neuropathies possibly result from a defect in the axon-myelin adhesion secondary to the binding of IgM on an epitope of MAG directly involved in cell-cell adhesion.